topic 8

• Tumour suppressor genes produce proteins which slow cell division/cause them to self destruct if errors occur in DNA replication.

  Mutations in the tumour suppressor genes stop this protein being produced... cell division is uncontrolled/ mutated cells would not be identified/destroyed
• Proto-oncogenes produce protein involved in initiation of DNA replication/mitosis

  Mutations in the proto-oncogenes result in this process being permanently activated... cells divide uncontrollably
• Tumour cells:

  • have irregular shape
  • nucleus is larger/multiple
  • don't produce all the proteins needed to function correctly
  • rapid rate of mitosis
• When tumour suppressor genes are hypermethylated...genes not transcribed/proteins to slow cell division aren't made....cells divide uncontrollably...tumours can develop
• mutated proto-oncogene is called an oncogene
• Hypomethylation of proto-oncogenes (causes them to act as oncogenes)....gene permanently switched on... increasing production of proteins which initiate cell division..... cell divides uncontrollably ...tumour
• Increased methylation (+ve) of DNA(-ve) inhibits transcription.

  • causes DNA to coil tightly around histones... preventing transcriptional factors from binding
• Decreased acetylation of associated histone proteins on DNA inhibits transcription.

  • if acetyl groups (-ve) are removed from DNA- histones become more positive/ attracted more to the phosphate group on DNA (-ve)
  • DNA/ histones more strongly associated and hard for the transcription factors to bind
• Totipotent cells- are able to divide into any type of body cell (only present in mammals in the first few cell divisions of an embryo)
• Pluripotent- (after totipotent-> embryonic become pluripotent)- can specialise into any cell in the body but placenta cells
• Multipotent- can differentiate into a few different types (ie/ found in bone marrow)
• unipotent- differentiate into one type
• Epigenetics- heritable changes in gene function; without changes to the base sequence of DNA
• Increased methylation could lead to cancer:

  • Methyl groups could be added to both copies of tumour suppressor gene
  • transcription of tumour suppressor genes is inhibited
  • leading to uncontrolled cell division
• Transcription factors bind to DNA/promotor sequence and either:

  • stimulate RNA polymerase/ transcription (activators)
  • inhibit RNA polymerase/ transcription (repressors)
• A transcription factor is a molecule that moves from cytoplasm to DNA: binds to specific target gene, blocks binding of RNA polymerase to DNA
• osmoreceptors are located in the hypothalamus
• When the water potential of the blood decreases water will move out of the osmoreceptors by osmosis. This causes the cells to decrease in volume
• The secretion of ADH (affects urine production of kidneys):

  • increases permeability of membrane/ cells of collecting duct/ distal convoluted tube
  • ...more water absorbed from DCT/collecting duct
  • smaller volume of urine
  • urine produced is more concentrated
• Removal of urea from blood:

  • Hydrostatic pressure (efferent arteriole/smaller diameter)
  • causes ultrafiltration at Bowman's capsule/glomeruli
  • Through the basement membrane
  • Enabled by small size of urea molecule
  • Urea is not reabsorbed in PCT/ loop of Henle/ DCT
• Urea is concentrated in the filtrate as:

  • Ions actively transported out into medulla (distal convoluted tubule/ collecting duct/ascending loop of henle)
  • ......increase in ion conc lowers water potential in the medulla
  • Reabsorption of water by osmosis (proximal convoluted tubule/ descending loop of henle)
• Lack of insulin affects the reabsorption of glucose in the kidneys:

  • High conc of glucose in blood
  • High conc in tubule/filtrate
  • Reabsorbed by facilitated diffusion/ active transport...(conc gradient not maintained)
  • Requires proteins/carriers
  • These are working at max rate/are saturated
  • Not all glucose in reabsorbed, some lost in urine
• Long loop of henle is an adaptation to living in desert conditions:

  • more water from filtrate is reabsorbed by osmosis from collecting duct
  • increased surface area
  • Na/Cl ions are absorbed from filtrate in ascending limb
  • gradient established in medulla
• Secretion of large amount of ADH are an adaptation of living in desert conditions:

  • Makes cells/ membrane of collecting duct/DCT more permeable
  • inserts aquaporins in plasma membranes
  • more water then absorbed